The overall objective of this proposal is to evaluate the therapeutic potential of a novel immunosuppressant protein produced by tick salivary glands. Ixodes scapularis, the black-legged tick, circumvents the host's immune response by multiple mechanisms as it obtains its blood meal. Salp 15 is a protein identified by screening a tick salivary gland cDNA library. Recombinant Salp 15 inhibits the proliferation and activation of CD4+ T cells in vitro, and is also active in vivo. However, recombinant Salp 15 is less active than the native form of the protein found in saliva. In phase I experiments, the primary structure of native Salp 15 will be determined. This information will be used to synthesize a new form of recombinant Salp 15 whose amino acid sequence matches precisely that of the native protein. The activity of this new recombinant protein will be determined in vitro and in vivo. Milligram amounts of this new recombinant Salp 15 suitable for use in animals will be purified. The activity of this protein will be tested in an animal model of human disease, namely murine Lyme arthritis. In Phase II experiments the activity of Salp 15 will be tested in additional animal models of human disease.